Infectious Complications of Antibody-Drug Conjugates: A Review of Safety Data from FDA-Approved Agents

With fifteen agents now FDA-approved and indications expanding into earlier treatment lines, antibody-drug conjugates (ADCs) represent a rapidly growing class of targeted cancer therapeutics. Despite their selective mechanism of action, infectious complications are clinically significant and have been flagged as a disproportionate safety signal in post-marketing surveillance. This review characterizes the infection risk profiles of all fifteen FDA-approved ADCs through systematic extraction of prescribing information and pivotal trial safety data, and examines the pathophysiological mechanisms, antigen-specific clinical patterns, and evidence-based prophylaxis strategies applicable to this class.

Calicheamicin-based agents carry the highest infection burden, with grade ≥ 3 infection rates exceeding 30-47% and near-universal severe neutropenia. CD30- and CD79b-targeting vedotin conjugates are associated with opportunistic infections-including progressive multifocal leukoencephalopathy and Pneumocystis jirovecii pneumonia-through mechanisms beyond myelosuppression, particularly T-cell immune surveillance disruption and bystander-effect lymphotoxicity. Solid tumor ADCs demonstrate lower overall infection rates with distinct organ-specific patterns: genitourinary infections predominate with Nectin-4- and Tissue Factor-directed agents, whereas pulmonary events characterize HER2- and c-Met-targeted conjugates. Linker cleavability, drug-to-antibody ratio, and payload metabolism are identified as key pharmacological determinants of myelosuppressive and infectious risk. Infectious complications of ADC therapy are clinically significant but heterogeneous, with risk profiles primarily determined by target antigen, immunologic context, and concurrent treatment. These findings support the growing adoption of a combined prevention strategy incorporating disease-based risk stratification and drug-directed infection prophylaxis.